Abstract
In the 1990s, the application of immunotherapy approaches to target cancer cells resulted in significant clinical responses in patients with advanced malignancies who were refractory to conventional therapies. While early immunotherapeutics were focused on T cell-mediated cytotoxic activity, subsequent efforts were centered on targeted antibody-mediated anticancer therapy. The initial success with antibody therapy encouraged further studies and, consequently, there are now more than 25 FDA-approved antibodies directed against a range of targets. Although both T cell and antibody therapies continue to result in significant clinical responses with minimal toxicity, a significant subset of patients does not respond to immunotherapy and another subset develops resistance following an initial response. This review is focused on describing examples showing that cancer resistance to immunotherapies indeed occurs. In addition, it reviews the mechanisms being used to overcome the resistance to immunotherapies by targeting the tumor cell directly and/or the tumor microenvironment.
摘要
在20世纪90年代，应用免疫治疗方法针对癌细胞，对传统疗法难治的晚期恶性肿瘤患者产生了明显的临床效果。早期的免疫疗法集中在T细胞介导的细胞毒活性上，而随后的努力则集中在靶向抗体介导的抗癌疗法上。抗体治疗的初步成功促进了进一步的研究，因此，现在有超过25种FDA批准的针对一系列靶点的抗体。尽管T细胞和抗体疗法带来显著的临床效果和最小的毒性，但有相当一部分病人对免疫疗法无效，另一部分病人在最初的有效后出现耐药。这篇综述的重点是描述显示癌症对免疫疗法耐药确实发生的例子。此外，它还回顾了通过直接针对肿瘤细胞和/或肿瘤微环境来克服免疫疗法耐药的机制。
参考文献
Bonavida, B., & Chouaib, S. (2017). Resistance to anticancer immunity in cancer patients: potential strategies to reverse resistance. Annals of oncology: official journal of the European Society for Medical Oncology, 28(3), 457–467. Doi: 10.1093/annonc/mdw615.
